Heterobenzyl Chlorides as Linchpins for C–H Arylation via Sequential C–H Chlorination/Cross-Electrophile Coupling

Synthetic methods that use C-(sp³)-H bonds in carbon-carbon cross-coupling reactions are limited and often lack generality, particularly with substrates containing basic heterocycles. Here, we demonstrate the arylation of heterobenzylic C-H bonds by using heterobenzyl chlorides as linchpins that can undergo Ni-catalyzed cross-electrophile coupling with aryl iodides. The results show different reactivity for primary and secondary heterobenzyl chlorides and also show differences among secondary heterobenzyl chlorides at different positions on the heteroaromatic ring. The Ni-catalyzed conditions identified for each of these substrate classes ensure that the rate of heterobenzyl chloride activation complements the rate of aryl iodide activation. These methods are demonstrated with series of heterobenzyl chlorides and (hetero)-aryl iodides, providing a general strategy for C-(sp³)-H arylation.